- Person
- Max Perutz
- Lived
- 1914–2002
- Field
- Molecular biology
- From
- Austrian-British
The story
Haemoglobin exists in many variant forms. Some are found in other species, such as crocodiles and carp, which have adapted their haemoglobin to unusual habitats and ways of life. Others are mutant human haemoglobins that cause inherited blood disorders. In 1957 Vernon Ingram, working in the same Cambridge unit as Max Perutz, discovered that sickle cell anaemia is caused by a single amino acid change in the haemoglobin molecule.
Once Perutz and his colleagues had solved haemoglobin's three-dimensional structure, he could see where each change sat in the molecule and explain its effect. Francis Crick, writing his obituary, recalled his strong interest in the consequences of amino acid differences, both in the many known human mutants and in other species, and noted that in most cases the change in the molecule's behaviour could be explained once the change in sequence was known. Perutz studied the structural changes behind a number of haemoglobin diseases and how they affect the binding of oxygen.
He hoped the molecule could be made to act as a drug receptor, and that it might become possible to inhibit or reverse the effects of genetic errors such as those behind sickle cell anaemia. He set out this approach in his 1992 book Protein Structure: New Approaches to Disease and Therapy.
In later years he worked on how small molecules bind to haemoglobin, aiming to develop a clinically useful drug that would increase oxygen delivery to oxygen-starved tumours to help radiation therapy, and to tissues damaged by heart attacks. He was still doing this kind of research in his eighties, working in the laboratory almost every day.
His approach of reading disease from a molecule's structure, and then looking for chemicals that fit it, anticipated the structure-based drug design used today. When he died in 2002 the head of the Medical Research Council said his prize-winning work on protein structure was more relevant than ever as scientists sought to understand the mechanisms of disease.
Why it matters
Perutz's work helped establish the idea of molecular disease and pointed the way to structure-based drugs for inherited disorders.
About Max Perutz
Viennese refugee who spent 22 years solving the structure of haemoglobin, won the 1962 Nobel Prize and built the Cambridge laboratory where molecular biology came of age.
More about Max Perutz
- Max Perutz founded the unit where DNA's shape was foundIn 1947 Max Perutz obtained Medical Research Council support for a small unit to study biological molecules; Watson and Crick built their DNA model there in 1953.
- Max Perutz was also a pioneering glacier scientistIn 1938 Max Perutz joined a three-man expedition to study how snow becomes glacier ice in Switzerland, work that made him an expert on glaciers.
- Perutz explained how haemoglobin delivers oxygenIn 1970 Max Perutz proposed how haemoglobin works as a molecular machine, switching shape to pick up oxygen in the lungs and release it in the tissues.
- Max Perutz found the key to seeing protein structuresIn 1953 Max Perutz showed that attaching heavy atoms such as mercury to protein crystals solves the X-ray 'phase problem', making protein crystallography possible.
- In his eighties, Perutz took on Huntington's diseaseIn his final years Max Perutz studied Huntington's disease, showing that its age of onset is linked to the number of glutamine repeats, which form a 'polar zipper'.
- Perutz led a lab whose scientists shared 12 Nobel PrizesMax Perutz founded and chaired the MRC Laboratory of Molecular Biology in Cambridge from 1962 to 1979; its scientists have shared 12 Nobel Prizes.
- Max Perutz revealed the structure of haemoglobinIn 1959, 22 years after he began, Max Perutz determined the structure of haemoglobin, the blood's oxygen carrier, sharing the 1962 Nobel Prize in Chemistry.
Sources
- Max Ferdinand Perutz (obituary by Francis Crick) Physics Today
- Max Perutz Wikipedia
- Max Perutz American Crystallographic Association history
- MRC Laboratory of Molecular Biology Wikipedia
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